5-aza-2'-deoxycytidine induces apoptosis and inhibits tumour growth in vivo of FaDu cells, a specific HPVnegative HNSCC cell line.
5-aza-2'-deoxycytidine induces apoptosis and inhibits tumour growth in vivo of FaDu cells, a specific HPVnegative HNSCC cell line.
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DOI：
10.1371/journal.pone.0253756
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Fares F
中科院分区：
文献类型：
--
作者：
Miari R;Azzam N;Bar-Shalom R;Fares F
头颈部癌鳞状细胞癌(HNSCC)是世界上第六大常见癌症，每年导致超过60万例新诊断。传统上，HNCC与烟草和酒精接触有关；然而，在过去十年中，越来越多的头颈部癌症被归因于人类乳头瘤病毒(HPV)感染。5-氮杂-2‘-脱氧胞苷(5-azad)是治疗急性髓系白血病的有效化疗药物。临床前数据显示，5-aza抑制HPV(+)癌细胞的生长并增加细胞死亡。这些作用与减少HPV基因的表达、稳定TP53和激活依赖于TP53的细胞凋亡有关。本研究旨在检测5-azad对HPV(-)和p53基因突变的人鳞状细胞癌(FaDu)细胞生长的影响。体外检测5-azad对细胞存活率、细胞周期进程和诱导细胞凋亡的影响。在接种FaDu细胞的异种移植小鼠体内检测5-azad对肿瘤生长的影响。结果表明，5-azad在体外可降低FaDu细胞的存活率并诱导其凋亡。体内研究表明，5-azad通过抑制细胞增殖和诱导细胞凋亡来抑制接种FaDu细胞的移植瘤的生长。这些发现可能强调，5-azad通过TP53非依赖途径治疗HPV(-)HNSCC肿瘤是有效的。为了阐明5-azad在HPV(-)癌细胞中的作用机制，还需要进一步的研究。
Head and neck cancer squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, resulting in over 600,000 new diagnoses annually. Traditionally, HNCC has been related to tobacco and alcohol exposure; however, over the past decade, a growing number of head and neck cancers are attributed to human papillomavirus (HPV) infection. 5-Aza-2’-deoxycytidine (5-AzaD) was demonstrated as an effective chemotherapeutic agent for acute myelogenous leukaemia. Preclinical data revealed that 5-aza inhibits growth and increases cell death of HPV(+) cancer cells. These effects are associated with reduced expression of HPV genes, stabilization of TP53, and activation of TP53-dependent apoptosis. The aim of the present study is to test the effect of 5-AzaD on growth of human squamous cell carcinoma (FaDu), a HPV(-) and p53 mutated cells, in vitro and in vivo. The effect of 5-AzaD on cell viability, cell cycle progression and induction of apoptosis was tested in vitro. The effect of 5-AzaD on tumour growth in vivo was tested using xenograft mice inoculated with FaDu cells. The results indicated that 5-AzaD reduced cell viability and induced apoptosis in FaDu cells in vitro. In vivo studies revealed that 5-AzaD suppresses the growth of tumours in xenograft mice inoculated with FaDu cells through inhibition of proliferation and induction of apoptosis. These findings may emphasis that 5-AzaD is effective in treatment of HPV(-) HNSCC tumours through TP53 independent pathway. Future studies are needed in order to clarify the molecular mechanism of action of 5-AzaD in HPV(-) cancer cells.
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